Induction of prostacyclin formation by sodium n-butyrate in a cloned epithelial liver cell line.
The effect of sodium n-butyrate on prostaglandin synthesis in cultured cells was examined. Exposure of BC-90 cells, a clone of an epithelial rat liver cell line, to 1 mM sodium n-butyrate for 40 h induced prostacyclin production. Prostacyclin synthesis was proved by demonstrating: (1) production of labeled 6-ketoprostaglandin F1 alpha by treating [14C]arachidonic acid pre-labeled cells with calcium ionophore A23187, (2) production of unstable substance that inhibited adenosine diphosphate-induced platelet aggregation, and (3) conversion of [14C]arachidonic acid to 6-ketoprostaglandin F1 alpha in homogenates of n-butyrate-treated cells. Untreated control cells showed negligible prostaglandin synthesis. Untreated cell homogenates did not convert [14C]arachidonic acid to any prostaglandins, but they converted [14C]prostaglandin H2 to prostacyclin. Induction of prostacyclin production by n-butyrate was also demonstrated with cells that had been treated with acetylsalicylic acid before n-butyrate treatment in acetylsalicylic acid-free medium. Incorporation of [3H]acetylsalicylic acid by sodium n-butyrate-treated cells increased in accordance with treatment time, while that of untreated cells did not change during culture. There was no difference in the phospholipase A2 activities of n-butyrate-treated and -untreated cells. From these findings, the possibility that n-butyrate induced prostacyclin in BC-90 cells through induction of fatty acid cyclooxygenase activity is discussed.
D015121:6-Ketoprostaglandin F1 alpha; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002999:Clone Cells / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis
D002087:Butyrates; D011453:Prostaglandins; D011460:Prostaglandins F; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases